The long term goal of this research has been to characterize the neuronal circuitry involved in the presynaptic control of the synaptic effectiveness of primary afferents in the vertebrate spinal cord and the role played by presynaptic inhibition in sensory-motor integration. The proposed experiments are aimed to disclose the selectivity of the supraspinal control exerted on the spinal pathways mediating the primary afferent depolarization (PAD) of individual muscle spindle and tendon organ afferents and how this control is modified following a peripheral nerve lesions. The following hypothesis will be tested: 1. The synaptic effectiveness of the segmental and ascending collaterals of the same muscle afferent can be selectively controlled by supraspinal structures. We will examine the effects produced by intracortical and surface anodal stimulation of the cerebral and cerebellar cortex and of the bulbar reticular formation on the intraspinal threshold of two collaterals of the same afferent fiber, one in the intermediate and/or motor nucleus and the other in Clarks's column or in the dorsal column nuclei. 2. The last-order GABAergic interneurons that mediate PAD comprise at least two functionally distinct subpopulations of neurons. Experiments will be made to a) establish the synaptic (GABAergic) nature of the monosynaptic PAD produced by graded intraspinal microstimulation either in one or in two collaterals of the same muscle afferent fiber, and b) to characterize the segmental and descending inputs acting on the last-order GABAergic interneurons that are activated by the intraspinal microstimulation. 3. The changes in PAD patterns that are produced after crushing a peripheral nerve are restricted to the lesioned afferent fibers. We have shown that stimulation of the bulbar reticular formation (RF) produces very little PAD in intact muscle spindle afferents. However, 1-3 months after a peripheral nerve crush., RF stimulation produces large PAD in afferent fibers reconnected with muscle spindles. The selectivity of these changes will be tested by recording the PAD elicited by at least two different descending inputs (reticulo- and cortico-spinal) on lateral and medial (MG) gastrocnemius afferents in preparations in which only the MG nerve was crushed 1-3 months previously. We will also examine if the PAD produced at that time is associated with presynaptic inhibition. 4. The PAD-mediating interneurons and the intermediate nucleus interneurons mediating the nonreciprocal inhibition are associated with different subpopulations of dorsal hon neurons. Previous work has shown that there are at least two subpopulations of intermediate nucleus interneurons mediating non-reciprocal inhibitory actions. One of them produces only postsynaptic glycinergic inhibition and the other pre- and postsynaptic GABAergic inhibition. By recording the intraspinal field potentials that are associated to the activity of single interneurons and the interactions of these potentials with potentials produced by stimulation of segmental and descending pathways, we will be able to disclose the functional relationship between individual interneurons and other sets of spinal neurons.